This is a post on the science on thyroid antibodies and symptoms. It was not until I had been thyroid sick for 7 years, that a doctor mentioned antibodies to me. That my high anti-TPO levels could affect my well being. This was in 2007. That is quite early for a doctor to be aware of this. Most doctors TODAY refuse to believe that antibodies can affect quality of life. At least here in Denmark. Many doctors won’t even test for antibodies. The Danish endocrinologists claim, antibodies are only important in terms of diagnosing. And they don’t even know, that some people with autoimmune thyroid disease (AITD) don’t have antibodies at all. You can read more about that here.
I have no doubts, that antibodies affect us. Our immune system is not in balance. It’s my conviction, that a lot of fatigue is caused by imbalances in our immune systems. I also believe, our gut health plays into it, and some people have what’s called a leaky gut. I am not going into that in this post though.
Everybody with AITD knows, we are not who we were. But it’s difficult to say what’s what. Is it all the years with mistreatment? All the years with too low FT3 even though we were on thyroid medication? Or can the antibodies also contribute to the fatigue we often feel?
It’s usually after years of being sick that we start understanding our disease. At that point we learn about optimal thyroid levels, which you can read about here, here.
And we get the right medication that will give us these levels. But we often still feel tired. It could be antibodies, though us with Ord’s atrophic have low antibody levels after our thyroid has shrunk. It is not my impression, we are feeling better than the people with true Hashimotos, who often have high antibody levels even after years of disease. It could be, it’s our compromised immune system that is the problem. I know for myself, after I started with Low dose naltroxene (LDN) link, the fatigue improved immensely. And what LDN does, is regulate the T regulator cells. Which play a big role in our AITD.
I will look at the science in this post. To wake people up to the fact, that it’s important. Here in Denmark, people have enormously high antibody levels. I am talking 20/30 000 IU/L. And they are being told by their doctors, it does not matter. It does matter!
You can show your doctor some of these studies, if he or she doesn’t let you test for antibodies.
I am very disappointed though, or I would have been were it not for the fact that I have reads heaps of studies on thyroid issues. The participants are very often low on their thyroid levels. And it is the same in most of these studies. So we can’t really say what’s what, hypothyroid or antibodies.
I almost didn’t bother writing this post after I had looked at the science. But even if we understand, the participants are hypo thyroid, your doctor won’t understand it. So to have a case for antibody testing, these studies work fine.
Less symptoms in thyroiditis without antibodies.
You might think, that everyone with an autoimmune thyroiditis have thyroid antibodies. This is not the case. Some has what’s called “serum negative thyroiditis”. They don’t have antibodies, at least not anti-TPO and anti-TG. I don’t think they test for TSHR antibodies. Hypothyroid can also have TSHR antibodies, the blocking and cleavage kind. I write about that here.
Anyway, one sees that these people have thyroiditis when doing an ultrasound. They have the hypoechoic pattern one sees in thyroiditis. Hypoechoic areas are dense tissue that does not send signals back on an ultrasound. Literally “not many echoes”. It looks like a giraffe pattern. These hypoechoic areas are caused by lymphocytic infiltration.
It’s this infiltration that damages our thyroids. Not anti-TPO or anti-TG. It’s mainly T and B lymphocytes that ruin our glands. I write about that here.
These patients would never be diagnosed. I think very few doctors are aware, that you can have serum negative thyroiditis. Even though they are an estimated 5% of all hypo thyroid patients.
Anyway, the point here, is that studies show, these patients have less symptoms and even better thyroid levels than patients with antibodies. This is an open study, everybody can read it. Many studies lie behind pay walls. (1)
In the study, they talk about “chronic autoimmune thyroiditis” (CAT) and “serum negative autoimmune thyroiditis” (SN-CAT). They look at 55 people with SN-CAT, 7 men and 48 women. In the control group, there were 110 people, 12 men and 98 women. They all had CAT.
It’s a retrospective study, that is, one looks backwards. The participants were included based on an elevated TSH. These numbers are from when they were diagnosed.
Anthropometric and clinical parameters in patients with CAT and SN-CAT. Data are shown as mean±s.d. unless otherwise stated.
|CAT (Ab+)||SN-CAT (Ab−)||P value|
|No. of patients||110||55|
|Age at diagnosis (years)||47.3±14.7||47.7±16.6||0.869|
|TSH (μU/ml) (median and range)||6.8 (4.2–58.0)||5.8 (4.1–27.0)||0.0007|
|Overt/subclinical hypothyroidism||23/87 (20.9%)||3/52 (5.4%)||0.012|
|Thyroid volume (ml)||11.2±6.5||8.1±3.7||0.001|
|Thyroid volume (ml) (median and range)||10 (3–62)||8 (2–20)||0.00003|
|Nodule (yes/no)||25/85 (22.7%)||14/41 (25.4%)||0.697|
|Goiter >20 ml||3 (2.7%)||0 (0%)||0.551|
Bold characters indicate significant differences. I have added the pmol/L results. That is the most common European units.
As you can see from the numbers, those with thyroid antibodies have lower thyroid levels. 20,9% have either subclinical hypothyroid or hypothyroid. Only 5,4% in the SN CAT group.
I don’t know how they have made the division between subclinical and hypothyroid. I suspect based only on the TSH. But I see, that many have a too low FT3, with the lowest at 3,9 pmol/L /2.5 pg/ml. Which is hypothyroid.
Many more than the 20,9% are hypo thyroid in my opinion. The median TSH in the CAT group is 6.8, with the lowest TSH in the group is 4,2! And in the CN CAT group the median TSH is 5,8 with the lowest at 4,1. So everybody is hypothyroid. A normal TSH is around 1,5. You can find info on this on my optimal thyroid levels that I link to over.
Those with antibodies have larger thyroid glands.
Anti-TPO interferes with the TPO enzyme (2). If this is the only reason that the CAT group have lower thyroid levels than the SN CAT. I think it is a weakness with the study, that we don’t know how much antibodies they have. We only know that they have anti-TPO >32.7UI/ml and anti-TG >33.6UI/ml.
The study tells us, that one has more symptoms and lower thyroid levels with antibodies than without. That is not the same, as antibodies cause more symptoms no matter the thyroid levels. But it does say, that thyroiditis without antibodies is less severe.
In many of the studies on symptoms and antibody load, one uses a questionnaire called SF-36. You can read the questions here, https://orthotoolkit.com/sf-36/
It’s a subjective assessment of how one’s disease affect you in your everyday life; physically, emotionally, socially and just generally.
Two studies on anti-TPO
This is a study where they look at changes in life quality after surgery for benign goiter. (3) The study is best know under the name Ott, where Regina Promberger is co-author. I couldn’t assess that study, that is, it’s behind a pay wall. But I have looked at the follow up study they did after 36 months.
It’s very important to read the whole study, not just the abstract. You need to look at the actual numbers. And as you will see from these two studies, all the participants are not euthyroid. Which the authors claim.
They include people with a TSH between 0,25 and 4.20 µU/ml. People with a TSH over 2 are not thyroid healthy. You can find studies on this on the optimal thyroid levels post over. As you see from the numbers, some of the participants are hypothyroid with a FT3 of 3,1 pmol/L (2 pg/ml) and some are hyperthyroid with a FT3 of 7.5 pmol/L (4.8 pg/ml). They have the reference range for FT3 3,1 -7,5 pmol/L. I have never seen a range go up to 7,5. The highest I have seen is 7. You are quite hyper with a FT3 of 7,5. The same with the FT4, which in the participants ranged from 0,9 ng/dl to 1,9 ng/dl. Those at the outer edges here are hypothyroid and hyperthyroid.
Table 1 Preoperative patient characteristics (n 248)
Age (y) 56 (21–82)
BMI (kg/m2) 26.5 (17.0–47.6)
Preoperative TSH (mU/mL) 1.1 (0.7–2.5)
Preoperative fT3 (pmol/L) 4.6 (3.1–7.5)
Preoperative fT4 (ng/dL) 1.3 (0.9–1.9)
Preoperative TPO-Ab (IU/mL) 8.0 (0–600.0)
Patients with thyroid hormone
supplementation 61 (24 .6%)
Data are expressed as median (range) or as number (percentage).
As you can see, there are both very underweight and very overweight people included. A good indication for hypo-and hyperthyroid. The authors believe these women are all euthyroid. NOT!
You see that the cut off point for anti-TPO is at 120 IU/ml. You might find that high. Here in Denmark they have set it at 35 IU/ml . The reason for this cut off point, is that when they looked at the glands they had taken out, it was at 120 they found the typical Hashimotos damage. That is interesting in itself. But of course, one cannot set the cut off point for Hashimotos where the damage is already done. I don’t understand that thinking.
But it is interesting, that they say, those with anti-TPO over 120 IU/ml have much more symptoms:
Chronic fatigue, dry hair, chronic irritability, chronic nervousness, a history of breast cancer and early miscarriage, and lower quality-of-life levels were significantly associated with anti-TPO levels exceeding the cut-off point (p < 0.05).
I mean, we saw in the study above, that those without antibodies had a better quality of life. But these are very serious symptoms, even implicating a connection between breast cancer and antibodies, as well as miscarriage. But don’t take this for proven. They don’ t know about thyroid levels, so everything they find must be taken with a pinch of salt. Could be that those with higher antibodies also had lower thyroid levels. But even so, these are serious symptoms.
They also found, that some people had histological Hashimotos without antibodies. 29 patients had Hashimotos, so only 11,7%.
There wasn’t a great change in pre- and post operative quality of life. Except for “bodily pain”, which decreased. But for those with Hashimotos, quality of life increased more. They are talking about, if thyroid removal can be an option in the treatment of Hashimotos. As all thyroid antibodies are produced inside the thyroid. But the results were not so clear cut as for them advising thyroid removal as a treatment option.
The symptoms increased from 4 to 5 right after the surgery, so people felt worse after surgery. And this difference was even greater in those with higher antibody levels.
But at follow up 12 and 33 months later, one didn’t find great changes in quality of life. But the higher their preoperative antibody levels, the more benefit they had from the surgery.
What these scientists aren’t aware of, is that the gland supports the conversion of T4 to T3 in the body. People without a thyroid need more L-thyroxine than hypothyroid people with a thyroid.(4)
They did a follow up study 3 years later. In that study, they didn’t even test their thyroid levels! What a mistake, a big flaw with the study. These scientists obviously don’t know why people generally feel worse after thyroidectomy. There are 2 main reasons:
- The gland produces T3.
- The gland supports the conversion of T4 to T3 elsewhere in the body.
I am pretty sure, they have a lower FT3 3 years after than they had before surgery. But they have become free from symptoms from the goiter. But it can be unwise to remove the whole gland unless you have to, that is if you have a very large goiter or cancer. These were patients from Austria. As the authors write themselves, it’s an iodine deficient area and this is most likely the reason for their goiter. So, if you have a goiter, try supplementing with iodine before deciding on surgery. You can learn how to do that safely on my post. And if you decide on surgery, remove as little as necessary.
But because of this fact, it’s difficult to measure the effect of antibodies. Because the participants have lost their gland and we don’t know their present thyroid levels. Anyway, there are other ways of reducing antibody levels, and I will write about that in my next post.
Anti-TPO and symptoms
This is a study (6) where they wanted to look at quality of life and anti-TPO. They looked at differences between people with hypothyroid who use Levothyroxine and people with hypothyroid who don’t. They used that SF-36 questionary.
What they found, was that euthyroid people with Hashimotos had poorer quality of life than thyroid healthy people.
You can see the numbers here:
Hashimotos TSH 2.40±1.20 FT4 1.20 (1.0-1.30)
FT4 15.4 pmol/L
Control TSH 1.78±0.86 FT4 1.26(1.06-1.34)
( FT4 16.2 pmol/L)
LT4 minus TSH 2.67±1.27 FT4 1.13 (1.0-1.23)
(FT4 14.5 pmol/L)
LT4 plus TSH 2.10±1.05 FT4 1.20(1.12-1.35)
(FT4 15.4 pmol/L)
There are no units given for the FT4 measurements. Very unprofessional. But it’s got to be ng/dl. I have converted into pmol/L as well, as this is the unit in many countries.
As you can see, in the Hashimotos group, some had a very low FT4 of 1.20 ng/dl. And in the control group, some had 1.26 ng/dl. So hypo really. But could be their FT3 was still adequate, we don’t know. When scientists don’t test FT3, one knows immediately, that they don’t know what they are doing. And of course, they don’t know either, that people taking T4 meds usually need to have a FT4 high in reference in order to have a mid range FT3. Because very few hypothyroid convert as well as the thyroid healthy. Some do. You can read about thyroid levels and how to estimate how well you convert on the optimal thyroid levels post.
The group called LT4 minus, are people with Hashimotos NOT on thyroid medication. Some of them are obviously hypo, and should be on meds. And many of those ON meds, from the LT4 plus group, are also hypo. Generally speaking, one should not have a TSH over 1 when taking T4 meds. An old person might lie a little higher. Here the mean TSH is 2.1, with some having a TSH of 3.15! I mean, they are heavily under dosed.
They claim, they have found that quality of life is lower in what they call the euthyroid Hashimotos group compared to “healthy” controls. But these people aren’t euthyroid. They also think they have found something very interesting, in that the quality of life does not differ that much between the LT4 minus group and the LT4 plus group. They draw the conclusion, that T4 medicine doesn’t help that much. OMG. No, it does not help when you don’t get enough of it. I give up!
I haven’t included all the numbers. I don’t find it very interesting, as the participants are hypothyroid. It’s an open study, that you can find via the link.
It’s so stupid, one feels like crying. And doctors probably swallow this, most of them. You can say, it’s a good thing, that there is focus on the effects of antibodies. But the results are not accurate, when people are hypothyroid, they have so many symptoms, we cannot know what’s what.
Anti-thyroglobulin and symptoms
They looked at many parameters in this study. (7) The participants were Hashimotos patients not on thyroid medication. They tested their TSH, FT4, FT3, anti-TG, anti-TPO and thyroid gland volume. They also looked at age, body surface(?), hypo symptoms and blood pressure. Many had goiter, and others had the damages typical of Hashimotos.
Again, again, they are all hypothyroid. Here are the numbers:
TSH, mIU/L 3.71 (2.08–6.19)
T3, nmol/L 1.55 (1.3–1.8)
T4, nmol/L 101 (85.65–115)
fT4, pmol/L 11.9 (10.1–12.8)
TgAb, IU/ml 131 (31.9–439)
TPOAb, IU/ml 224 (23.4–654)
Thyroid volume, cm3 10.58 (7.96–14.58)
Age, years 37.89 (28.34–47.97)
BSA, m2 1.81 (1.7–1.93)
Number of symptoms, N 3 (1–7)
Systolic blood pressure, mmHg 118 (110–130)
Diastolic blood pressure, mmHg 70 (65–80)
The numbers in parenthesis are the highest and the lowest. They all have a TSH that is too high, a T3 that is too low as well as a too low FT4.
A normal T3 is 2.24 nmol/L. This is total T3, not free T3. A normal T4 is around 112 nmol/L. So some of the subjects had a normal T4. But their FT4 is too low.
What do they find? They found, that anti-TG levels had the greatest influence on symptom load. They claim, anti-TG levels have more to say for symptom load than hormone levels! OMG! That is because they are all hypothyroid, only more or less.
It’s maybe interesting that they find a greater correlation between symptoms and anti-TG than anti-TPO. They find that anti-TG gives more symptoms like frail hair, facial edemas and hoarse voice. But these symptoms would be greatly alleviated with better thyroid levels, and some iodine .
Some of the subjects also have small thyroids, normal size for a female is 10 to 15 ml. 1 ml is 1 cm3. so some of the subjects have a shriveled gland. A sure sign of hypothyroid of the atrophic kind.
Both anti-TPO and anti-TG.
This is a study where they test for both anti-TPO and anti-TG. (8) Again they use the SF-36 questionnaire.
They had 84 participants with Hashimotos. They call them euthyroid, but of course, not everybody is. They were included on the basis of blood tests and ultrasound of the gland. 13 of them were antibody negative, but one could see from their glands, that they had AITD. They write, that they left out people with subclinical hypothyroidism. 52 of the 84 were taking thyroid medicine. 94% were women, 6% were men.
|Sex (female), n (%)||79 (94)|
|Patients with thyroid hormone supplementation, n (%)||52 (62)|
|Patients with comorbidity, n (%)||18 (21)|
|Age (y), mean ± standard deviation||41.82 ± 12.16|
|TSH (μU/mL), median (25th–75th percentile)||1.89 (0.96–3.22)|
|fT4 (ng/dL), median (25th–75th percentile)||1.10 (0.99–1.19)|
|Anti-TPO (IU/mL), median (25th–75th percentile)||287.19 (22.72–762.20)|
|Anti-Tg (IU/mL), median (25th–75th percentile)||24.82 (3.38–160.07)|
- Anti-Tg = anti-thyroglobulin antibody; Anti-TPO = anti-thyroperoxidase antibody; fT4 = free thyroxine; TSH = thyroid stimulating hormone. Fra Uysal et al (7).
Their TSH lies between 0.96 and 3.22. We don’t know at what time of day they were tested. But we know that 3.22 means hypothyroid no matter what. Their FT4 lies between 0.99 ng/dl (12.7 pmol/L) and 1.19 ng/dl (15.3 pmol/L). As you can see, FT4 is way too low considering, 62% of them are taking thyroid meds. We know that most people on T4 meds need a FT4 high in range. So once again, many of the symptoms are due to them being hypothyroid.
They consider everyone who has a TSH between 0.35-4.94 IU/ml and FT4 between 0.70-1.48 ng/dl. 0.70 ng/dl is 9 pmol/L. One is practically dead with a FT4 like that. At least very sick.
What did they find?
They claimed to have found:
- There is a correlation between each life quality score and antibody levels.
- There is no statistical correlation between thyroid levels and antibodies.
- There is no correlation between quality of life and TSH or FT4.
When they didn’t wake up at number 3, one knows for sure, they know nothing about hypothyroidism. I would be chocked if I hadn’t read so many studies. You cannot say anything about symptoms and thyroid levels when everyone is too low on their thyroid levels. Everyone who has a thyroid disease, know, thyroid levels have everything to say for quality of life. Only people without hypothyroidism can believe, that antibody levels have a greater impact on one’s symptom level than thyroid levels. I find it weird, that they don’t understand, cells must have T3. They should try living with low FT3 levels, see how it feels!
But this study does say something about how antibodies affect us. The participants were both antibody negative and positive. 18 without anti-TPO, 66 with. 24 without anti-TG, 60 with.
AND THESE WERE MATCHED FOR THYROID LEVELS, AGE, SEX AND COMORBIDITY. ONE FOUND THAT THOSE WHO HAD ANTIBODIES HAD LOWER QUALITY OF LIFE THAN THOSE WITHOUT.
That was what they found in our first study as well. Even though there are serious flaws with these studies, it’s pretty certain that antibodies causes symptoms. And that is common sense as well.
People have VERY high antibody levels here in Denmark. Like 20 to 30 000 IU/ml! They are being told by their doctors, it does not matter. It’s therefore very important for me, to get this message out. And I will look at the science on how to reduce one’s antibody levels in my next post.
Antibodies and depression and anxiety
In this next study, researchers looked at the correlation between mood and anxiety disorders and anti-TPO levels in 2 villages in Sardinia. There were 222 subjects. We don’t know the participants’ individual thyroid levels in this study (9). They have a FT4 between 6-16 pmol/L (0.46 – 1.2ng/dl) , FT3 between 2.8-5.6 pg/ml (4.3-8.6 pmol/L) and TSH between 0.3-3 IU/ml . They also looked at their glands with ultra sound.
This is an Italien study. Seems they have very strange thyroid ranges. The FT4 goes from very low to only 1.2 ng/dl, and the FT3 goes from 2.8 pg/ml. Which I find very good. Because no thyroid healthy person has a FT3 under 2.8 pg/ml, a normal FT3 is from 3.05 pg/ml. And in all ranges I have seen to date, lower end of FT3 range is always way too low. So this is very positive with these Italien ranges. But it goes way too high though, I wonder if it is a typo. People are very hyperthyroid with a FT3 of 5.6 pg/ml. The TSH range goes to 3, which is also very good. As no healthy person has a TSH over 2, and the wide ranges we see in TSH are due to the fact that many undiagnosed hypothyroid people are included in the so called “normal” population they base ranges on. And all thyroid patients know, what a big problem the wide ranges for TSH is for us in terms of getting diagnosed. So very strange and unusual ranges. Their anti-TPO cut off point was also low, 20 IU/ml.
But they don’t include the objects’ thyroid results, which obviously is a big weakness. But we do know, no one has a FT3 under 2.8 pg/ml, so no one is seriously hypothyroid. They compared them for gender and age, so weird to not look at their thyroid levels.
Anyway, they did find, that amongst patients with depression or anxiety disorders, people with elevated anti-TPO had a higher prevalence of these disorders. That’s interesting.
The psychiatric disorders and the autoimmune reaction seem to be rooted in a same (and not easy correctable) aberrancy in the immuno-endocrine system.
What they are saying, is that mood and anxiety disorders seems to be caused by some flaws in the immuno-endocrine system. They have no proof of this. Another example of researchers making conclusions that their findings do not support. We have no idea, why people with elevated anti-TPO seem to be more prone to at least some types of mood and anxiety disorders. It can very well be, that the antibodies makes you feel worse. As far as I know, we don’t know that much about whether anti-TPO affects other parts of the body besides interfering with the TPO enzyme in the thyroid. Or if it’s “just” the dysfunction in the immune system that affect our wellbeing. It can also be as they say, thyroid autoimmunity and some psychiatric disorders are caused b the same dysfunction in the immune system.
As a psychologist, and human being, I don’t believe it’s that simple. I don’t think anxiety and depression are caused by the immune system. I think it’s very much more complicated. You certainly can become depressed when your immune system is poor or dysfunctional. It makes for fatigue and exhaustion. I know this from my own experience. How much stronger and better I have felt since starting with Low dose naltroxene (LDN) 8 years ago. LDN goes in and regulates the T regulator cells.
But I also know, that depression and anxiety stem from trauma and painful experiences. I guess most people know this. I, at least, have become so much happier in later years. After having worked on all my issues for years. And people with AITD have a higher rate of trauma in their lives than the thyroid healthy.
Here is a study on thyroid antibodies and depression (10) It’s a study on people with a major depression diagnoses. They included 30 depressed patients and 60 controls. This was major depression, that is, serious depression.
They tested for 3 different thyroid antibodies. anti-TPO, anti-TG and blocking TSHR abs. They are called Thyroid Binding Inhibitory Immunoglobulins (TBII). They BLOCK instead of stimulate the TSH receptors. The result is hypothyroid, and not hyperthyroid. There are actually 3 kinds of TSHR abs. Few people are aware of this. You can read more about it here, Antibodies, part 3, TSHR abs, TRAb
They claim, that when one tests for thyroid levels, one doesn’t find a clear correlation between hypothyroid and depression. But this is of course, because they don’t know what are normal thyroid levels.
There were 30 patients in the experimental group (10 men and 20 women) aged between 42±11. And 60 people in the control group (25 men and 5 women) aged 41±9. 4 of the 30 (13%) had a little elevated TSH. 12 (26%) had elevated anti-TPO. 5 (16%) had elevated TBII. No one had elevated anti-TG.
They call anti-TPO, microsomal antibodies. This is an old word for anti-TPO. In the table under, they call TSHR abs TBII, anti-TPO TMA, anti-TG TA. In case you want to read the study your self. I must admit, I find the study confusing and difficult to understand. There are so many tables and they have correlated for several factors, Only not the most important; thyroid levels. Kill me now.
I see from this graph, that several of the participants are hypothyroid.
You see here, that several have a FT4 around 12 pmol/L. That is hypo. A normal FT4 will be from 14 pmol/L. Their TSH does not look very high. But then we don’t know the time of day for the labs. If it is taken in the afternoon, then it can be as much as 1 units lower than in the morning. I don’t understand that TSH axis either, it says 100.00? It must be 10. But even if they mean 10, the axis is all wrong, and I cannot read it. Some also have a high FT4.
The reason I include this study, is that they tested for TBII abs and found, that people with depression had higher levels of TBII abs. When you have blocking TSHR abs, TBII, you will become hypothyroid. And you may be MORE hypo than hypothyroid patients without TBII.
That can be the reason why the depression is correlated with TSHR abs’ levels. It can also be something to do with the antibodies themselves. We have TSH receptors in other tissues besides the thyroid gland . Maybe the TSHR abs do other things in the body besides blocking the TSH from adhering to the TSH receptors. Or it can be the dysfunction in the immune system. These are just hypotheses and speculations on my part.
The authors also speculate quite a bit. We must keep in mind, this is clinical depression. That is serious depression. But they claim, there is no need to test thyroid levels in depressed people. .
They also write, that it is a known thing, that subclinical hypothyroid suffer more from depression than controls. As a psychologist, I know that many people presenting with depression turn out to by hypothyroid. Testing thyroid levels must be a first step. But then of course, you have to know what are normal levels and doctors don’t.
They divide the depression in two categories, melancholic and atypical.
Melancholic is a more hyper like state. One loses one’s appetite, looses weight, sleeps poorly, is anxious, fear the future, things are worse in the morning.
Atypical present with the opposite; one eats a lot, sleeps a lot, is tired and feels best in the morning.
They write, depressed people had higher levels of TBII than controls. and that people with atypical depression had higher anti-TPO than the controls.
They also say this:
It is reported that most patients with depression may have alterations in their thyroid function including slight elevation of the serum FT4, blunted TSH response to thyrotropin-releasing hormone (TRH) stimulation, and loss of the nocturnal TSH rise and this may reflect brain hypothyroidism in the context of systemic euthyroidism.
When I try to go into the study they refer to for this info, I don’t find any thyroid levels reported in that study. They just state these claims as fact. But it might be true. And it is interesting, if depressed people don’t have a higher TSH at night. Healthy people have higher TSH and higher thyroid levels at night. They call this brain hypothyroidism. Low thyroid levels locally in the brain, causing disturbances in one’s mood. But we don’t know that much, as we don’t have the FT3 levels. These people could have had a low FT3 both day and night.
This mechanism could be the explanation, why some of these people have a slightly elevated FT4 in the graph over. This is interesting, and I believe true. T4 is important for the brain.
It’s an interesting fact, that in Japan they have only 3% cases of Major depressive disorder (MMD). The number in the US is 16,9%. With all I know about iodine and iodine deficiency, I can’t help but think, iodine is the deciding factor in this. It’s unrelated to this topic per se, but being iodine replete is very important for one’s mood. I have a post on safe supplementation with iodine, Iodine for beginners
They also write, that some of the inflammatory processes are the same in depression and AITD.
a common neuroendocrine dysregulation involving cytokines might concur towards the pathogenesis of both affective disorders and autoimmune disease.
Note the might, I don’t think this is proven or certain. But it is certain, that the role of the immune system is great in so many diseases and conditions.
I like this study (10), as they are more humble and tentative than many others. They know something about thyroid disease and the participants aren’t hypothyroid.
Antibodies and hives
Many with hypothyroidism are plagued by itching. it can be very bothersome. Does thyroid antibodies play a part in this ailment? Yes, they do play a part.
I struggle with severe itching at times, so I know how bothersome it can be. There are many studies on this, and one has been aware of a connection between hives and hypothyroid since the 80ies.
The diagnosis of hives is set when
there is a rash, chronic or temporary with large, red rashes (erythematous) with welts and itching at least twice a week for 6 weeks.
I think that we lay people call any itchy rash that we perceive as caused by something, internal or external, for hives.
One divides the patients in two groups:
In about 60%, the hives is connected to serological factors. Elevated levels of immunoglobulin E(IgE) production. T cell induced cytokine production, increased secretion of histamine, prostaglandins, kinins and other proinflammatory substances.
In another group, the hives is connected to autoimmune reactions. The patients have antibodies to the IgE receptors and IgE itself. These antibodies cause an activation of basophile granulocytes and mast cells. This leads to secretion of histamine and an infiltration of cells that one usually sees in inflammation.
Among patients with urticaria, app. 25 to 30% have elevated thyroid antibodies. AND those with thyroid abs have more serious hives. This seems like a strong connection.
In this study (11), they included 145 women and 3 men in the experimental group. They all had chronic hives. 80 had angio edemas (welts). In the control group, they had 22 men and 13 men without hives. So the control group were much smaller.
But when I look at the labs of the two groups, I see that the control group contains some people who are hypothyroid. Some had FT3 at 4.1 pmol/L. That is not a healthy FT3. I have studies on normal thyroid levels on my Optimal thyroid levels post. But the main thing in this study, is the antibodies. And the hives group have much higher antibody levels than the controls.
I know the image is bad, but it proved quite difficult for me. I am just an amateur and I do everything on my site myself. Anyway, you see, people with hives have MUCH more thyroid antibodies. In the experimental group, 23 had elevated anti-TPO, 9 had elevated anti-TPO and anti-TG. 33 had been diagnosed with AITD.
The authors discuss, that people in the experimental group had low thyroid levels, but they don’t mention that people in the control group had even lower. I find that strange. But it’s certain, that people with hives had higher levels of antibodies. Unfortunately, they didn’t compare severity of hives with severity of antibody level.
They don’t think, that thyroid antibodies cause the hives, but that there is a connection. They don’t know the exact connection, but it is known, that thyroid antibodies can adhere to IgE on mastocytes with a release of histamine as a result.
In this study (12), they wanted to see if there is a connection between thyroid levels, the size of the gland and skin reactivity. Skin reactivity is a sign of over active mast cells.
I won’t go into too much details. They say they have tested for TSH, FT4, FT3, anti-TG and anti-TPO. But they don’t tell us the numbers. I have read the whole study; it’s not an open study.
They have 3 groups, one with Hashimotos patients, one with healthy subjects and one with goiter with nodules without thyroid antibodies. They employ two skin tests, they call them the old and the new. It is the ASST, autologus serum skin test. Where one simply scrape on the skin and look at the size and duration of the red mark one gets. A certain size, and one has overactive mast cells.
They found that ASST was negatively correlated with the size of the gland. That is, the smaller the gland, the more skin reactivity. More hives and more itching.
They write, that the study shows that the gland grows smaller in chronic AITD. But I can’t see that it shows this. They haven’t measured anything over time. This claim is not correct. The gland does not grow smaller in Hashimotos. It grows smaller when you have Ord’s or Ord’s atrophic. These are two variations of AITD. I will write a post on this at some point. It will be part of this series. These scientists don’t know this. .
This is not about antibodies as such, but the size of the thyroid. But I found it interesting, so included it. What I glean from this, is that people with Ord’s, people like me, will have more issues with hives. I do for sure.
I just have to mention quercetin here. It has helped a lot with my hives. It’s a plant flavonoid which you find in many fruits, vegetables and berries. It’s a natural antihistamine. I feel it has really helped with my hives. You have to take at least 1500 mg, and I take it every day.
And if you like me, get hives in certain situations, then it’s a good idea to also take some antihistamine in those situations. I don’t take antihistamine on a regular basis. I only take quercetin . But if I become acutely ill or I am about to have an operation, I also take regular antihistamines. As I always get hives in those situations. And then I itch for weeks afterwards.
If you have issues with hives, it can be a good idea to join one of the mast cell groups on FB or online. Or just read up on mast cell disease or watch some videos on You Tube.
It\s not that much to conclude on. As I have repeated again and again, the participants in these studies are usually hypothyroid. But in a couple of the studies, they have not too bad thyroid levels. All the studies say, antibodies causes symptoms. Unfortunately, it’s difficult to know whether it’s the thyroid levels or the antibodies. All of us who are hypothyroid, know how terrible we feel when our levels are too low.
But when we then have high antibody levels on top of that, we will feel even worse. Here in Denmark, I see people having enormously high anti-TPO levels, 20 000 to 30 000 UI/ml. You read that right. I never see such numbers elsewhere. If you have such levels, you really need to do all you can to get them down.
And the fact that we often itch and have rashes, is not strange. There is an established connection between Hashimotos/AITD and hives. One doesn’t know the cause, only that there is a connection. But it it the antibodies? I am not sure. In the last study, you saw, that it was the size of the gland that really played a big role. The smaller the gland, the more serious the hives. And we know, that all antibodies are produced inside the gland. You can read more about that here. So these people would have lower antibody levels than those with a larger gland. So at least for hives, antibodies do not seem to be as important as the size of the thyroid.
I can only say on my account, I have much more hives now that my gland is nearly gone. I had a pea left 5 years ago. And I have hardly any antibodies anymore either.
People with Hashimotos will always have higher levels of antibodies than us with Ord’s. The gland stays large, and keep on producing antibodies.
It’s for sure, people who have AITD without antibodies, are having less symptoms than those with antibodies. That is a pretty strong case for antibodies causing symptoms.
- M Rotondi et al. Serum negative autoimmune thyroiditis displays a milder clinical picture compared with classic Hashimoto’s thyroiditis. DOI: 10.1530/EJE-14-0147. https://pubmed.ncbi.nlm.nih.gov/24743395/
- V Kaczur. Effect of anti-thyroid peroxidase (TPO) antibodies on TPO activity measured by chemiluminescence assay. PMID: 9267319. https://pubmed.ncbi.nlm.nih.gov/9267319/
- R Promberger. Quality of life after thyroid surgery in women with benign euthyroid goiter: influencing factors including Hashimoto’s thyroiditis. DOI: 10.1016/j.amjsurg.2013.05.005. https://pubmed.ncbi.nlm.nih.gov/24070662/
- John M E Midgley. Variation in the biochemical response to l-thyroxine therapy and relationship with peripheral thyroid hormone conversion efficiency. doi: 10.1530/EC-150056. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4557078/
- J Ott, Hashimoto’s thyroiditis affects symptom load and quality of life unrelated to hypothyroidism: a prospective case-control study in women undergoing thyroidectomy for benign goiter. DOI: 10.1089/thy.2010.0191. https://pubmed.ncbi.nlm.nih.gov/21186954/
- Mehmet Muhittin Yalcin et al. Is thyroid autoimmunity itself associated with psychological
well-being in euthyroid Hashimoto’s thyroiditis? https://www.jstage.jst.go.jp/article/endocrj/64/4/64_EJ16-0418/_pdf/-char/en
- A Baric. Thyroglobulin Antibodies are Associated with Symptom Burden in Patients with Hashimoto’s Thyroiditis: A Cross-Sectional Study. https://doi.org/10.1080/08820139.2018.1529040. https://www.tandfonline.com/doi/full/10.1080/08820139.2018.1529040
- H B Yusal. Autoimmunity affects health-related quality of life in patients with Hashimoto’s thyroiditis. https://doi.org/10.1016/j.kjms.2016.06.006. https://onlinelibrary.wiley.com/doi/full/10.1016/j.kjms.2016.06.006
- M J Carta. The link between thyroid autoimmunity (antithyroid peroxidase autoantibodies) with anxiety and mood disorders in the community: a field of interest for public health in the future. https://bmcpsychiatry.biomedcentral.com/articles/10.1186/1471-244X-4-25#Tab2
- K N Fountoulakis et al. Thyroid function in clinical subtypes of major depression: an exploratory study. doi: 10.1186/1471-244X-4-6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC394331/
- M Czarnecka-Operacz et al. Thyroid function and thyroid autoantibodies in patients
with chronic spontaneous urticaria. doi.org/10.5114/ada.2017.72464. file:///C:/Users/User/Downloads/Thyroid_function_and_thyroid_autoantibodies_in_pat.pdf
- Z Turkoglu et al. Skin autoreactivity in Hashimoto’s thyroiditis patients without urticaria: autologous serum skin test positivity correlation with thyroid antibodies, sonographical volume and grading. DOI: 10.1684/ejd.2012.1711. https://pubmed.ncbi.nlm.nih.gov/22503840/